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Wednesday, August 20, 2008

ADVANTAGE: Who was actually in charge of R&D? And other questions...

Roy Poses addresses many of the controversial issues raised by the Annals of Internal Medicine article "The ADVANTAGE seeding trial: a review of internal documents" in "Bad Seed: the ADVANTAGE Trial of Vioxx."

I wish to raise a few additional questions:

The Wall Street Journal and others pointed out that Edward Scolnick, MD, President of Merck Research Labs and largely seen as the #2 official in the company, worried that the ADVANTAGE study risked disclosing data to the Food and Drug Administration that could cause problems for Vioxx.

"Small marketing studies which are intellectually redundant are extremely dangerous," Scolnick said. [i.e., they pose a danger of non-meaningful adverse results due to chance - ed.]

(a) Merck’s Executive Vice President, Science and Technology, (b) President, Merck Research Laboratories (“MRL”), (c) member of Merck’s Management Committee, (d) member of MRL’s Research Management Committee, (e) member of the board of directors of Merck.

This raises the following questions:

If the President of the Research Labs, ostensibly the head of R&D at the company, could not stop such a "seeding trial" study of a drug not yet released and/or its publication, then who was actually in charge of R&D?

Was the go-ahead for the study approved by erstwhile CEO Gilmartin? The Board?

Was there internal conflict at high levels over this and similar issues of control?

Why did Roger Perlmutter, MD, PhD, former Merck Executive Vice President of Worldwide Basic and Preclinical Research -- who was believed to be Merck Research Labs (MRL) leadership heir apparent -- suddenly leave Merck in 2001? Could it have something to do with perceived lack of control of the MRL President's office over pre-release drug studies?

What other such "seeding studies" on other drugs were conducted, and who authorized them?

Several corollary questions also arise:

Merck rationed access to tools essential for R&D and new drug discovery to its R&D scientists on the order of several million dollars annually. Tools the science heads themselves wrote were essential to R&D were being denied them despite my best efforts as Director of the MRL Science Libraries to end the rationing through a comprehensive and (I thought) compelling gaps analysis. As an example of one site head's beliefs, a VP of Medicinal Chemistry wrote a note about substantially increasing desktop access to cheminformatics tools such as CrossFire and SciFinder as well as other specialty databases (as did other R&D leaders):

"These applications are invaluable to the productivity of medicinal chemists in my department.CrossFire, in particular, is highly useful as the primary source for chemical information.Most new Ph.D. chemists whom we recruit are accustomed to using these tools to facilitate their research, and in fact, it is embarrassing that I have eight new Ph.D.'s who have arrived beginning last August who still do not have desktop access to CrossFire or SciFinder.I cannot overemphasize the value of having these tools accessible to chemists at their desktop, and I would urge you to expedite their deployment as quickly as possible."

This raises the questions:

Why were "seeding studies" that the head of R&D himself called "intellectually redundant" and "extremely dangerous" being funded, while the needs of R&D and new drug discovery in particular were being underfunded?

The budgetary decisions for these tools, I believed, were ostensibly being made by the VP of Research Computing in MRL, an IT person lacking a science or biomedical background (an issue for another time). What pressures was that person being put under from other departments - e.g., those running "seeding studies" - to cut essential R&D budgets?

Was the budget decision not to end rationing of advanced informatics tools necessary for new drug discovery actually made by the VP of Research Computing? Or was the decision made by someone else to siphon money for other purposes, who had a different agenda?

Is Merck's pipeline thin due to such decision making? Did the company sacrifice its future for immediate gratification, not realizing the whole scenario would implode when the drug, VIOXX, was found to have "previously unknown" harmful side effects, an issue which itself has been the topic of much controversy and billions in litigation?

Related to VIOXX, other questions that arise relative to rationing of informatics tools are:

Could the rationing of tools essential to drug scientists in any way have been related to a desire by someone to hobble their ability to explore the issues related to drug side effects?

Why were many in the company who previously had live access to the webcasted, periodic R&D Research Council meetings suddenly cut off from access in late 2002 or early 2003? What, exactly, did the company fear from dissemination of such discussions about R&D?

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